Diet restriction in mice causes a decrease in hippocampal choline uptake and muscarinic receptors that is restored by administration of tyrosine: interaction between cholinergic and adrenergic receptors influencing cognitive function

Nutr Neurosci. 2001;4(2):153-67. doi: 10.1080/1028415x.2001.11747359.


We have studied the effects of diet restriction (DR) to 60% and 40% of daily requirements, and tyrosine administration on cognitive function in mice, to define the nutritional-neurochemical interactions on autonomic tone involved in behavior and energy regulation. Cognitive function in the Morris Water maze was significantly impaired after 40% DR compared to both control and 60% DR. It was restored after tyrosine in association with increased M1 cholinergic and beta-adrenergic receptor function, and decreased alpha-adrenergic function. DR to 40% significantly decreased choline uptake (p <.05) and M1 receptor number (Bmax) (p <.05), without changes in affinity (Kd), choline acetyl transferase (ChAT) or acetyl cholinesterase (AChE) activity. Tyrosine administration significantly increased choline uptake (Bmax) (p <.05) and M1 density in the 40% DR (p <.01) without changes in affinity. ChAT activity was decreased after tyrosine--significantly after 40% DR (p <.05) while AChE was not affected. Both M1 mRNA and protein were not influenced by DR or tyrosine administration. Tyrosine hydroxylase mRNA was decreased significantly by 40% DR (p <.01). The effect of DR and tyrosine appeared to be both pre- and post-synaptic, indicating modulation of cholinergic activity by adrenergic tone. Nutritional effect on behavior and autonomic tone may have implications for the treatment of mood changes associated with weight loss and semi-starvation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biological Transport
  • Choline / metabolism*
  • Cognition / drug effects
  • Cognition / physiology*
  • Diet, Reducing*
  • Female
  • Hippocampus / metabolism*
  • Mice
  • Mice, Inbred Strains
  • Receptor, Muscarinic M1
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / physiology
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / physiology
  • Tyrosine / pharmacology
  • Tyrosine / therapeutic use*


  • CHRM1 protein, human
  • Receptor, Muscarinic M1
  • Receptors, Adrenergic, beta
  • Receptors, Muscarinic
  • Tyrosine
  • Choline